A large number of medical endoprostheses or implants for a range of applications is known from the prior art. Endovascular prostheses or other endoprostheses, for example stents, fasteners for bones, for example screws, plates or nails, surgical suture material, intestinal clamps, vessel clips, prostheses in the area of hard and soft tissue, and anchoring elements for electrodes, in particular pacemakers or defibrillators are understood as implants in terms of the present invention.
Stents used for treating stenoses (vessel constrictions) are used these days particularly frequently as implants. They have a body in the form of a punctured tubular or hollow-cylindrical grating, where required, open at both longitudinal ends. The tubular grating of such an endoprosthesis is inserted into the vessel to be treated and serves to support the vessel. Stents have proven themselves in particular for treatment of vessel diseases. Through the use of stents constricted regions in vessels can be widened, resulting in a gain in lumen. Using stents or other implants produces an optimal vessel cross-section primarily necessary for successful therapy, although the ongoing presence of this type of foreign body launches a cascade of microbiological processes which can result in a gradual increase in the stent and in the worst case scenario in vessel obstruction. An approach to solving this problem is to make the stent or other implants from a biodegradable material.
Biodegradation is understood to mean hydrolytic, enzymatic and other decomposition processes determined by metabolism in the living organism, caused especially by bodily fluids coming into contact with the biodegradable material of the implant and leading to gradual dissolution of the structures of the implant containing the biodegradable material. At a certain point the implant loses its mechanical integrity through this process. The term biocorrosion is used frequently, similarly to the term biodegradation. The term bioresorption includes subsequent resorption of the waste products through the living organism.
Materials suitable for the body of biodegradable implants can for example contain polymers or metals. The body can comprise several of these materials. A common characteristic of these materials is their biodegradability. Examples of suitable polymer compounds are polymers from the group cellulose, collagen, albumin, casein, polysaccharides (PSAC), polylactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D,L-lactide-co-glycolide (PDLLA-PGA), polyhydroxy butyric acid (PHB), polyhydroxy valerian acid (PHV), polyalkyl carbonates, polyorthoesters, polyethylene terephthalate (PET), polymalonic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids and their copolymers and hyaluronic acid. Depending on the preferred properties polymers can be present in pure form, in derivatized form, in the form of blends or as copolymers. Metallic biodegradable materials are based predominantly on alloys of magnesium and iron. The present invention preferably relates to implants the biodegradable material of which at least partially contains a metal, preferably iron, manganese, zinc and/or wolfram, in particular an iron-based alloy (hereinafter abbreviated as iron alloy).
In making biodegradable implants the attempt is made to control the degradability according to the intended therapy or application of the respective implant (coronary, intracranial, renal etc.). It is for example an important target range for many therapeutic applications that the implant loses its integrity in a period of four weeks to six months. In this case, integrity, that is mechanical integrity, is understood as the property, wherein the implant barely has mechanical losses relative to the undegraded implant. This means that the implant is still sufficiently mechanically stable that at the most the pressure has fallen for example only slightly to 80% of the nominal value. The implant can thus still comply with its chief function, keeping the vessel open, when integrity is present. Alternatively, the integrity can be defined by the implant being so mechanically stable that it has barely undergone geometric changes in its loaded state in the vessel, for example it does not noticeably slump, that is has at least 80% of the dilation to diameter under load, or in the case of a stent has barely begun supportive aspirations.
Implants with an iron alloy, in particular stents containing iron, are particularly cost-effective and easy to manufacture. For example, for treating stenoses these implants tend to lose their mechanical integrity or supportive effect after a comparatively long period, that is, only after a dwell time in the treated organism of ca. 2 years. This means that the collapse pressure in implants containing iron is reduced too slowly for this application over time. For other applications of implants containing iron, for example in orthopedics, the degradation period is short, however.
Various mechanisms of degradation control of implants are already described in the prior art. These are based for example on inorganic and organic protective layers or their combination, which set resistance against the human corrosion medium and the corrosion procedures running. Solutions known to date are distinguished by focusing on barrier layer effects based on spatial and the most defect-free separation of the corrosion medium from the metallic material. These result in the degradation time being prolonged. In this way the degradation protection is safeguarded by variously composed protective layers and by defined geometric distances (diffusion barriers) between the corrosion medium and the basic magnesium material. Other solutions are based on alloy constituents of the biodegradable material of the implant body, which influence the corrosion process through a shift of position in the electrochemical series. Further solutions in the area of controlled degradation cause break-off effects from application of physical (for example local modifications in cross-section) and/or chemical changes in the stent surface (for example locally and chemically variously composed multilayers). With the above solutions, however, there is mostly no success in placing the dissolution occurring via the degradation process and the resulting cell breaks in the stipulated time window. The consequence is variability of the degradation of the implant, which is begun either too soon or too late or excessive.
A further problem in connection with coatings also results from stents or other implants usually taking on two states, specifically a compressed state with a small diameter and an expanded state with a larger diameter. In the compressed state the implant can be introduced into the vessel to be supported by means of a catheter and positioned at the site to be treated. At the treatment site the implant is then dilated for example by means of a balloon catheter or transitions to the expanded state (with use of a shape memory alloy as implant material) for example by being heated to above a transition temperature. Due to this change in diameter the body of the implant is subjected to mechanical stress. Other mechanical stresses of the implant can occur during manufacture or with movement of the implant in or with the vessel, into which the implant is inserted. The drawback to the abovementioned coatings is that the coating of the implant tears during deformation (for example due to microtears developing) or is also partially removed, causing unspecified local degradation. Also, insertion and rate of degradation depend on the size and distribution of the microtears resulting from deformation, which cannot be controlled well as imperfections, leading to substantial scattering in degradation times.